In this review of all imaging studies concerning the staging of hilar cholangiocarcinoma, we found only 16 studies (primarily concerning CT only), including in total 448 patients. Although our aim was to compare the four individual investigations, this was not feasible because of the insufficient availability of adequate studies on MRI, ultrasound and PET/CT. Only data on CT were sufficient for pooling the findings. Pooled accuracy of CT for assessment of ductal extent of the tumour was 86%. Pooled sensitivity and specificity of CT were 89% and 92% for assessment of portal vein involvement, 84% and 93% for assessment of hepatic artery involvement, and 61% and 88% for assessment of nodal status, respectively.
The results of this systematic review should be interpreted with caution because of several limitations. Firstly, the included studies have limited methodological quality, as was detected by using the QUADAS tool (). Moreover, probably most importantly, the time between the index test and reference standard was mentioned in only 9 studies, and was less than 31 days in 7 studies. Therefore, misclassification due to progression of disease may have occurred [3
]. Results of studies reporting on diagnostic performance are hard to interpret without details on methodology, and consequently many QUADAS items were scored as unclear. New diagnostic studies should be reported, adhering to the Standards for Reporting of Diagnostic Accuracy (STARD) [13
]. The STARD initiative provides a checklist of items that should be included in the report of a study on diagnostic accuracy.
Secondly, a meta-analysis was not feasible for ultrasound, MRI and PET/CT owing to the low number of data sets and low number of patients in the data sets. Consequently, no comparisons could be made. Thirdly, heterogeneity of the studies was substantial, owing to differences in imaging technique (e.g.
for CT varying between 4- and 64-slice CT); study quality; small sample sizes in the studies (and consequent variability as a result of chance); and patient population (e.g.
differences in disease stage). To compensate for this problem, we performed random models to adjust for the heterogeneity. Fourthly, we found only two studies, including only 34 patients in total, that compared two imaging investigations in the same population [5
]. Ideally the diagnostic accuracy of competing imaging investigations is assessed in the same patient population. This enables a more accurate assessment of differences in investigations, and also should identify pros and cons more easily. Fifthly, another limitation could be publication bias. Because of the small number of studies, as well as small number of patients within the studies, we believe a funnel plot to investigate publication bias was not meaningful.
20 articles were excluded because no 2×2 contingency table could be extracted. An additional 22 of the 70 articles selected for full manuscript review were excluded because no specific hilar cholangiocarcinoma data could be retrieved. Often data regarding hilar cholangiocarcinoma patients are reported in combination with the findings in other bile duct cancers. Presumably, this is a result of the rareness of the disease, and consequent small patient numbers. From a molecular and cell biological point of view, the discussion is still ongoing as to whether bile duct cancers can be seen as one entity or should be separated according to their location (intrahepatic, hilar and distal) [14
]. Yet, from a radiological point of view, interpretation of vascular involvement is clearly different when assessing an intrahepatic tumour from when assessing a hilar tumour that grows directly adjacent to the vessels. Moreover, gallbladder cancer, which is known for its high likelihood of metastatic disease, is also frequently included in studies on bile duct cancer, which can significantly impede correct interpretation of results. Therefore, we believe that future diagnostic studies on bile duct cancer should separately report the specific hilar cholangiocarcinoma data in the publication.
In addition to the imaging investigations evaluated in this study, also more invasive techniques—such as endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, staging laparoscopy, endoscopic ultrasound, intraductal ultrasound and choledochoscopy—are used in some centres to improve staging of hilar cholangiocarcinoma. Yet, since the staging process starts with non-invasive imaging, we intentionally have not evaluated these techniques in this systematic review, and have focused on non-invasive imaging. Nonetheless, the staging accuracy for hilar cholangiocarcinoma patients could be improved, and exploratory laparotomies for unresectable patients could potentially be decreased by using these techniques.
Finally, ultrasound, CT, MRI and PET/CT are used nowadays alone or in various combinations with each other for staging of hilar cholangiocarcinoma, and for the choice for surgical resection with curative intent or a palliative treatment. As clearly shows, evidence on the staging accuracy of these investigations is limited, especially for MRI, ultrasound and PET/CT. Moreover, no adequate head-to-head comparative studies exist. As a result, an accurate comparison of the investigations and an evidence-based guideline cannot be made yet. Thus, it is of vital importance that future studies will provide this evidence. These studies ideally should have a prospective design, although because of the time required for prospective studies on this rare disease, well-designed retrospective studies could also be of importance. Furthermore, most evidence is available about the use of CT for staging of hilar cholangiocarcinoma, yet these studies have serious methodological flaws and small patient numbers. However—probably even more importantly—no criteria for involvement of adjacent structures (e.g.
of the portal vein) exist. For example, for pancreatic cancer several criteria for portal vein involvement, including the presence of tumour involvement exceeding 180° of the circumference of the portal vein, have been established [16
]. Hence, future CT studies on hilar cholangiocarcinoma should focus on radiological criteria that can accurately predict vessel involvement using contemporary scanners.
In conclusion, diagnostic accuracy studies of CT, MRI, ultrasound or PET/CT for staging of hilar cholangiocarcinoma patients are sparse, often with a low number of patients giving moderate methodological quality. Therefore, there is a need for new methodologically solid studies. Owing to the lack of evidence, an adequate comparison of the various investigations was not feasible. Most evidence is available regarding staging with CT, which seems to have acceptable accuracy for assessment of ductal extent, portal vein and hepatic artery involvement (sensitivity and specificity ranging between 84% and 90%). The sensitivity of CT for nodal status, however, seems to be low (61%).